Detection of zinc translocation into apical dendrite of CA1 pyramidal neuron after electrical stimulation.
Translocation of the endogenous cation zinc from presynaptic terminals to postsynaptic neurons after brain insult has been implicated as a potential neurotoxic event. Several studies have previously demonstrated that a brief electrical stimulation is sufficient to induce the translocation of zinc from presynaptic vesicles into the cytoplasm (soma) of postsynaptic neurons. In the present work I have extended those findings in three ways: (i) providing evidence that zinc translocation occurs into apical dendrites, (ii) presenting data that there is an apparent translocation into apical dendrites when only a zinc-containing synaptic input is stimulated, and (iii) presenting data that there is no zinc translocation into apical dendrite of ZnT3 KO mice following electrical stimulation. Hippocampal slices were preloaded with the "trappable" zinc fluorescent probe, Newport Green. After washout, a single apical dendrite in the stratum radiatum of hippocampal CA1 area was selected and focused on. Burst stimulation (100Hz, 500microA, 0.2ms, monopolar) was delivered to either the adjacent Schaffer-collateral inputs (zinc-containing) or to the adjacent temporo-ammonic inputs (zinc-free) to the CA1 dendrites. Stimulation of the Schaffer collaterals increased the dendritic fluorescence, which was blocked by TTX, low-Ca medium, or the extracellular zinc chelator, CaEDTA. Stimulation of the temporo-ammonic pathway caused no significant rise in the fluorescence. Genetic depletion of vesicular zinc by ZnT3 KO showed no stimulation-induced apical dendrite zinc rise. The present study provides evidence that synaptically released zinc translocates into postsynaptic neurons through the apical dendrites of CA1 pyramidal neurons during physiological synaptic activity.
Suh
Sang Won
SW
Department of Neurology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, CA 94121, USA. sang.suh@ucsf.edu
D000818:Animals; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002614:Chelating Agents / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D005029:Ethylenediamines / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017966:Pyramidal Cells / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D015032:Zinc / Q000378:metabolism*
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002614:Chelating Agents; D005029:Ethylenediamines; D018690:Excitatory Amino Acid Agonists; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C491177:Slc30a3 protein, mouse; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D013779:Tetrodotoxin; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D007608:Kainic Acid